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Consequences of reduced production of NO on vascular reactivity of porcine coronary arteries after angioplasty: importance of EDHF
Author(s) -
Thollon Catherine,
FournetBourguig Marie Pierre,
Saboureau Delphine,
Lesage Ludovic,
Reure Hélène,
Vanhoutte Paul M,
Vilaine Jean Paul
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704828
Subject(s) - angioplasty , cardiology , coronary arteries , medicine , artery
The consequences of the reduced production of nitric oxide (NO) by cells from regenerated endothelium were investigated by measuring membrane potential of smooth muscle cells (SMCs), isometric tension and cyclic nucleotides content in porcine coronary arteries with intimal thickening, four weeks following angioplasty. Under basal conditions, SMCs of coronary arteries with regenerated endothelium were depolarized by 10 mV. This depolarization was associated with 82% decreased level of cGMP without alteration in cAMP. Sodium nitroprusside (SNP, 1 μ M ) repolarized SMCs of the previously denuded coronary arteries. This repolarization was abolished by 1H‐[1,2,4]‐oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ, 10 μ M ) and not suppressed by glibenclamide (10 μ M ), iberiotoxin (IbTX, 100 n M ) and the combination of charybdotoxin (ChTX, 40 n M ) plus apamin (100 n M ). Four‐aminopyridine (4‐AP, 1‐5 m M ) generated spontaneous rhythmic activities only in coronary arteries with regenerated endothelium which were abolished by SNP. Nevertheless, 4‐AP did not suppress the repolarization induced by SNP. In vascular segments with regenerated endothelium, contracted with prostaglandin F 2α (PGF 2α ), relaxation to bradykinin (BK, 30 n M ) was unaltered despite a reduced production of cGMP (−70%). Indomethacin (10 μ M ) plus N ω ‐nitro‐ L ‐arginine ( L ‐NA, 30 μ M ) reduced relaxation (−12% and −35% for native and regenerated endothelium, respectively) but did not abolish it. The hyperpolarizations induced by BK were not altered by the presence of indomethacin and L ‐NA and were unchanged in segments with regenerated endothelium. These data are consistent with a contribution of impairment in NO production to the depolarization of SMCs. Nevertheless, EDHF responses to BK are sufficient to maintain a normal relaxation after angioplasty.British Journal of Pharmacology (2002) 136 , 1153–1161. doi: 10.1038/sj.bjp.0704828